Drug Prevention and Control of Ventilator-Associated Pneumonia

Ventilator-associated pneumonia (VAP) is one of the most prevalent and serious complications of mechanical ventilation, which is considered a common nosocomial infection in critically ill patients. There are some great options for the prevention of VAP: (i) minimize ventilator exposure; (ii) intensive oral care; (iii) aspiration of subglottic secretions; (iv) maintain optimal positioning and encourage mobility; and (v) prophylactic probiotics. Furthermore, clinical management of VAP depends on appropriate antimicrobial therapy, which needs to be selected based on individual patient factors, such as previous antibacterial therapy, history of hospitalization or mechanical ventilation, and bacterial pathogens and antibiotic resistance patterns. In fact, antibiotic resistance has exponentially increased over the last decade, and the isolation of a multidrug-resistant (MDR) pathogen has been identified as an independent predictor of inadequate initial antibiotic therapy and which is significantly associated with increased mortality. Multiple attempts were used in the treatment of VAP, such as novel antibacterial agents, inhaled antibiotics and monoclonal antibodies. In this review, we summarize the current therapeutic options for the prevention and treatment of VAP, aiming to better management of VAP in clinical practice

SphK1/S1P Mediates PDGF-Induced Pulmonary Arterial Smooth Muscle Cell Proliferation via miR-21/BMPRII/Id1 Signaling Pathway

Background/Aims: The underlying molecular mechanisms involved in sphingosine kinase 1 (SphK1)/sphingosine 1-phosphate (S1P) mediation of platelet-derived growth factor (PDGF)-induced pulmonary arterial smooth muscle cell (PASMC) proliferation are still unclear, and the present study aims to address this issue. Methods: Small interfering RNA (siRNA) and microRNA inhibitor transfection was performed to block the expression of SphK1, bone morphogenetic protein receptor II (BMPRII) and microRNA-21 (miR-21). Gene expression levels of SphK1, BMPRII and inhibitor of DNA binding 1 (Id1) were detected by immunoblotting, miR-21 expression level was examined with qRT-PCR, and S1P production was measured by ELISA. Additionally, PASMC proliferation was determined by BrdU incorporation assay. Results: Our results indicated that PDGF increased the expression of SphK1 protein and S1P production, up-regulated miR-21 expression, reduced BMPRII and Id1 expression, and promoted PASMCs proliferation. Pre-silencing of SphK1 with siRNA reversed PDGF-induced S1P production, miR-21 up-regulation, BMPRII and Id1 down-regulation, as well as PASMC proliferation. Pre-inhibition of miR-21 also blocked BMPRII and Id1 down-regulation as well as PASMC proliferation caused by PDGF. Knockdown of BMPRII down-regulated Id1 expression in PASMCs. We further found that inhibition of PI3K/Akt and ERK signaling pathways, particularly ERK cascade, suppressed PDGF-induced above changes. Conclusion: Our study indicates that SphK1/S1P pathway plays an important role in PDGF-induced PASMC proliferation via miR-21/BMPRII/Id1 axis and targeting against SphK1/S1P axis might be a novel strategy in the prevention and treatment of pulmonary arterial hypertension (PAH)

Financial Risk Early-Warning Model Based on Kernel Principal Component Analysis in Public Hospitals

Public hospitals are facing the dual pressure of coping with external medical market competition and performing public health duties. Due to the influence of various risk factors, public hospitals are facing increasing financial risks. How to effectively prevent and control financial risks and maintain the normal operation and sustainable development of the hospital is a very important topic that needs to be studied in the development of public hospitals. Because the traditional principal component analysis method only pays attention to the global structural features and ignores the local structural features, a financial risk early-warning model based on improved kernel principal component analysis in public hospitals is proposed to improve the ability of risk assessment. The core ideas of the method in this paper for financial risk forecasting are as follows: the nonlinear features of the financial data are firstly extracted under different conditions, and then the feature matrix and the optimal feature vector are calculated to construct the distance statistics so as to determines the threshold by kernel density estimation; finally the Fisher discriminant analysis is used for similarity measurement to identify the risk types. Through experiments on the financial data of a number of public hospitals and listed companies, the experimental results verify the feasibility and effectiveness of the method used in this paper for financial risk analysis. This further shows that this research has a certain display significance

The impact of shared governance on the adverse mood of parturients with gestational hypertension and perinatal indicators of newborns

This study aimed to investigate the effect of shared governance on the adverse mood of parturients with gestational hypertension and perinatal indicators of newborns. A total of 318 patients with gestational hypertension treated in our hospital were enrolled as study subjects and were divided into a study group (200 cases) and a control group (118 cases) using double-blind, controlled and randomised methods. Before intervention, the systolic blood pressure (SBP), diastolic blood pressure (DBP), Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD) and Quality of Life Scale (SF-36) scores did not differ significantly between the two groups (p>.05). After intervention, the study group had lower SBP, DBP, HAMA and HAMD scores and higher SF-36 scores than the control group (p<.05). The neonates in the study group experienced a lower incidence of adverse outcomes than those in the control group (p<.05). Shared governance can regulate blood pressure and improve mood and quality of life in parturients with gestational hypertension. It can also reduce the incidence of adverse events in newborns during the perinatal period. Impact Statement What is already known on this subject? Gestational hypertension is the development of hypertension in pregnant women after 2 or 20 weeks of gestation and is characterised by headache, dizziness, nausea and swelling of the lower legs. Early intervention is key to improving maternal and neonatal prognosis. Shared governance is an emerging model of participatory decision-making in which nurses are empowered to make decisions about clinical practice standards, quality improvement, staff and professional development, and research, aiming to cultivate the patients' sense of responsibility for their health. What do the results of this study add? This study demonstrated that shared governance can regulate maternal blood pressure and improve maternal adverse mood, maternal quality of life and reduce the incidence of perinatal adverse events in the newborn, indicating the potential of shared governance and may promote the clinical application of shared governance. What are the implications of these findings for clinical practice and/or further research? This study starts with adverse mood of parturients and perinatal outcomes of newborns, and demonstrates in detail the impact of shared governance in nursing interventions on parturients with gestational hypertension and neonates. The data are detailed and reliable, providing certain clinical references for follow-up research

Expressions of MMP-12, TIMP-4, and Neutrophil Elastase in PBMCs and Exhaled Breath Condensate in Patients with COPD and Their Relationships with Disease Severity and Acute Exacerbations

Objective. The purpose of this study was to compare matrix metalloproteinase-12 (MMP-12), neutrophil elastase (NE), and tissue inhibitor of metalloproteinase-4 (TIMP-4) in peripheral blood of patients with chronic obstructive pulmonary disease (COPD) and controls. At the same time, MMP-12, NE, and TIMP-4 in exhaled breath condensate (EBC) were also evaluated. Methods. Peripheral blood and EBC samples from COPD patients and healthy controls were collected. In serum and EBC, MMP-12, NE, and TIMP-4 proteins were detected by enzyme-linked immunoassays. The mRNA expression levels of MMP-12, NE, and TIMP-4 in peripheral blood mononuclear cells (PBMCs) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Results. The concentration of TIMP-4 protein in EBC was lower in patients with COPD (P<0.001). MMP-12 (P=0.046), NE (P=0.027), and TIMP-4 (P=0.005) proteins in serum of patients with COPD showed higher levels of concentration. The mRNA of MMP-12 (P=0.0067), NE (P=0.0058), and TIMP-4 (P=0.0006) in PBMCs of COPD patients showed higher expression levels. Compared with stable patients, mRNA expression level of NE (P=0.033) in PBMCs of patients with acute exacerbation of COPD was increased. There were differences in the ratio of MMP-12/TIMP-4 in PBMC (P=0.0055), serum (P=0.0427), and EBC (P=0.0035) samples between COPD patients and healthy controls. The mRNA expression of MMP-12 (r=−0.3958, P=0.0186) and NE (r=−0.3694, P=0.0290) in COPD patients was negatively correlated with pulmonary function. However, the mRNA expression of TIMP-4 (r=0.2871, P=0.0945) in PBMCs was not correlated with the FEV1 of the pulmonary function. Serum MMP-12 level was positively correlated with the MMP-12 level in EBC (P=0.0387). The level of TIMP-4 in serum was not correlated with the level in the EBC sample (P=0.4332). Conclusion. The expression levels of MMP-12, NE, and TIMP-4 in PBMCs and serum were elevated in COPD patients. In PBMCs of COPD patients, the mRNA expression level of NE may predict acute exacerbation, and MMP-12 mRNA expression level may be used to reflect the severity of airflow limitation. However, to better assess their diagnostic or prognostic value, larger studies are necessary

Association between risk of asthma and gene polymorphisms in CHI3L1 and CHIA: a systematic meta-analysis

Abstract Background Previous studies have indicated that chitinase 3-like 1 (CHI3L1) gene rs4950928 polymorphism and acidic mammalian chitinase (AMCase or CHIA) gene rs10494132 polymorphism are associated with the risk of asthma. However, the results are inconsistent because of small sample size and varied ethnicity and age in studies. Therefore, a systematic meta-analysis was important to clarify the effect of CHI3L1 rs4950928 polymorphism and CHIA rs10494132 variant on asthma risk. Methods An electronic literature search was conducted to identify all the eligible studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and sensitivity analysis as well as publication bias were assessed to investigate the associations. All statistical analyses were performed using STATA 12.0. Results Eight published articles with 10 case-control studies were included, 5 studies were of CHI3L1 rs4950928 polymorphism and another 5 studies involved CHIA rs10494132 polymorphism. Overall, no significant association was found between CHI3L1 polymorphism and asthma susceptibility. After stratified according to ethnicity, CHI3L1 rs4950928 variant was associated with decreased asthma risk in Caucasians (GG + GC vs. CC: OR = 0.621, 95% CI = 0.484–0.797, P = 0.000; GC vs. CC: OR = 0.612, 95% CI = 0.470–0.796, P = 0.000; G vs. C: OR = 0.696, 95% CI = 0.567–0.856, P = 0.001). When stratified population by age, there was no association in children under all genetic models. As for CHIA rs10494132 polymorphism, no evidence of association between CHIA rs10494132 polymorphism and asthma risk was identified. Furthermore, subgroup analysis by ethnicity revealed a positive correlation between CHIA rs10494132 polymorphism and asthma risk among Asians (TT vs. TC + CC: OR = 1.476, 95% CI = 1.071–2.032, P = 0.017; T vs. C: OR = 1.326, 95% CI = 1.024–1.717, P = 0.032). Additionally, in the subgroup analysis conducted according to age, CHIA rs10494132 variant was also found to be associated with the increased risk of asthma in children (TT vs. TC + CC: OR = 1.472, 95% CI = 1.067–2.030, P = 0.019; T vs. C: OR = 1.320, 95% CI = 1.016–1.713, P = 0.037). Conclusions The G allele of CHI3L1 rs4950928 might be a protective factor against the development of asthma. However, the rs10494132 polymorphism of CHIA might be a risk factor for asthma

AS-703026 Inhibits LPS-Induced TNFα Production through MEK/ERK Dependent and Independent Mechanisms.

Chronic obstructive pulmonary disease (COPD) is characterized by intense lung infiltrations of immune cells (macrophages and monocytes). Lipopolysaccharide (LPS) activates macrophages/monocytes, leading to production of tumor necrosis factor α (TNFα) and other cytokines, which cause subsequent lung damages. In the current study, our results demonstrated that AS-703026, a novel MEK/ERK inhibitor, suppressed LPS-induced TNFα mRNA expression and protein secretion in RAW 264.7 murine macrophages, and in murine bone marrow-derived macrophages (BMDMs). Meanwhile, TNFα production in LPS-stimulated COPD patents' peripheral blood mononuclear cells (PBMCs) was also repressed by AS-703026. At the molecular level, we showed that AS-703026 blocked LPS-induced MEK/ERK activation in above macrophages/monocytes. However, restoring ERK activation in AS-703026-treated RAW 264.7 cells by introducing a constitutive-actively (CA)-ERK1 only partially reinstated LPS-mediated TNFα production. Meanwhile, AS-703026 could still inhibit TNFα response in ERK1/2-depleted (by shRNA) RAW 264.7 cells. Significantly, we found that AS-703026 inhibited LPS-induced nuclear factor κB (NFκB) activation in above macrophages and COPD patients' PBMCs. In vivo, oral administration of AS-703026 inhibited LPS-induced TNFα production and endotoxin shock in BALB/c mice. Together, we show that AS-703026 in vitro inhibits LPS-induced TNFα production in macrophages/monocytes, and in vivo protects mice from LPS-induced endotoxin shock. Thus, it could be further studied as a useful anti-inflammatory therapy for COPD patients

Knockdown of AMPKα2 Promotes Pulmonary Arterial Smooth Muscle Cells Proliferation via mTOR/Skp2/p27Kip1 Signaling Pathway

It has been shown that activation of adenosine monophosphate-activated protein kinase (AMPK) suppresses proliferation of a variety of tumor cells as well as nonmalignant cells. In this study, we used post-transcriptional gene silencing with small interfering RNA (siRNA) to specifically examine the effect of AMPK on pulmonary arterial smooth muscle cells (PASMCs) proliferation and to further elucidate its underlying molecular mechanisms. Our results showed that knockdown of AMPKα2 promoted primary cultured PASMCs proliferation; this was accompanied with the elevation of phosphorylation of mammalian target of rapamycin (mTOR) and S-phase kinase-associated protein 2 (Skp2) protein level and reduction of p27Kip1. Importantly, prior silencing of mTOR with siRNA abolished AMPKα2 knockdown-induced Skp2 upregulation, p27Kip1 reduction as well as PASMCs proliferation. Furthermore, pre-depletion of Skp2 by siRNA also eliminated p27Kip1 downregulation and PASMCs proliferation caused by AMPKα2 knockdown. Taken together, our study indicates that AMPKα2 isoform plays an important role in regulation of PASMCs proliferation by modulating mTOR/Skp2/p27Kip1 axis, and suggests that activation of AMPKα2 might have potential value in the prevention and treatment of pulmonary arterial hypertension